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Biomedical subjects

S Naito

Publications and source records attributed to S Naito.

At least 109 records · Page 6Linked to original sources

Accumulation of intracellular platinum is correlated with intrinsic cisplatin resistance in human bladder cancer cell lines.

We investigated the mechanism of intrinsic resistance to cisplatin in human transitional cell cancer (TCC) using 7 human bladder cancer cell lines, which were derived from untreated TCC of the urinary bladder. The sensitivity to cisplatin was different from cell line to cell line, and a 15-fold difference was observed between the most sensitive line and the most resistant line. No significant correlation was observed between the content of intracellular glutathione and the resistance to cisplatin. In contrast, a positive correlation was seen between intracellular cisplatin accumulation and cisplatin resistance. The expression of drug resistance-related genes including glutathione S-transferase pi, gamma-glutamyl-cysteine synthetase, multidrug resistance-1, multidrug resistance-associated protein, DNA topoisomerase I, topoisomerase II, human canalicular multispecific organic anion transporter, and thioredoxin was not significantly related to cisplatin resistance. These data suggest that intracellular cisplatin may contribute to intrinsic cisplatin resistance and may therefore be a useful biomarker to predict cisplatin sensitivity in human untreated TCC.

Carcinoma, Transitional Cell↗

Antitumor activity of interleukin-12 against murine bladder cancer.

PURPOSE: We investigated the antitumor activity of interleukin-12 (IL-12) against MBT-2, a murine bladder carcinoma, to clarify whether or not IL-12 is effective against urothelial tumors. MATERIALS AND METHODS: MBT-2, a murine carcinogen-induced, poorly differentiated transitional cell carcinoma of C3H/He origin, was used. Three or 10 days after the subcutaneous administration of MBT-2 cells, C3H/He mice were injected intraperitoneally with IL-12 five times per wk. for 2 wk. Tumor growth was measured twice weekly. Spleen cells from the C3H/He mice that had rejected MBT-2 after the IL-12 treatment were examined for MBT-2-specific cytolytic T lymphocytes (CTL) activity and cytokine production. RESULTS: Tumor growth and acceptance was obviously suppressed when C3H/He mice were treated with IL-12 from 3 days after the tumor inoculation. In the spleen cells from the C3H/He mice that had rejected MBT-2, MBT-2-specific CTL activity and secretion of IL-2 and interferon (IFN)-gamma were clearly detected. However, the established MBT-2 tumor cells were not rejected when C3H/He mice were given IL-12 from 10 days after the tumor inoculation, although the tumor growth was transiently suppressed during the IL-12 treatment. CONCLUSION: These data demonstrate that IL-12 is considerably effective against murine bladder cancer and suggest the clinical application of IL-12 against human bladder cancer.

Adjuvants, Immunologic↗

[Significance of exercise-induced ST segment depression in patients with myocardial infarction involving the left circumflex artery: evaluation by exercise thallium-201 myocardial single photon emission computed tomography].

The significance of exercise-induced ST segment depression in patients with left circumflex artery involvement was investigated by comparing exercise electrocardiography with exercise thallium-201 single photon emission computed tomography(Tl-SPECT) and the wall motion estimated by left ventriculography. Tl-SPECT and exercise electrocardiography were simultaneously performed in 51 patients with left circumflex artery involvement(angina pectoris 30, myocardial infarction 21). In patients with myocardial infarction, exercise-induced ST depression was frequently found in the V2, V3 and V4 leads. In patients with angina pectoris, ST depression was frequently found in the II, III, aVF, V5 and V6 leads. There was no obvious difference in the leads of ST depression in patients with myocardial infarction with ischemia and without ischemia on Tl-SPECT images. In patients with myocardial infarction, the lateral wall motion of the infarcted area evaluated by left ventriculography was more significantly impaired in the patients with ST depression than without ST depression(p < 0.01). Exercise-induced ST depression in the precordial leads possibly reflects wall motion abnormality rather than ischemia in the lateral infarcted myocardium.

Aged↗

Hand assisted laparoscopic radical nephrectomy for renal carcinoma using a new abdominal wall sealing device.

PURPOSE: We report our initial experience with a hand assisted laparoscopic radical nephrectomy for patients with renal carcinoma, and compare our results to those of conventional open radical nephrectomy. MATERIALS AND METHODS: The clinical data on 6 consecutive patients who underwent hand assisted laparoscopic radical nephrectomy for stage T1N0M0 renal cell carcinoma were reviewed. We performed hand assisted laparoscopic surgery using the new LAP DISC* abdominal wall sealing device. We compared the results of this procedure with those of conventional open radical nephrectomy in 12 patients with stage T1N0M0 renal cell carcinoma. RESULTS: The hand assisted laparoscopic radical nephrectomy for renal carcinoma was successfully performed without any major or minor complications in all 6 patients. Mean operation time for the laparoscopic group was significantly longer than that for the open surgery group (303 minutes versus 224 minutes, p = 0.0042). However, no significant difference was observed in mean estimated blood loss for the 2 groups (264 ml. in the laparoscopic group versus 341 ml. in the open surgery group). The frequency of parenteral analgesia postoperatively in the laparoscopic group was significantly lower than that in the open surgery group (16.7% versus 75.0%, p = 0.043). In addition, the laparoscopic group seemed to recover more rapidly than the open surgery group. The abdominal wall sealing device was easy to attach to the abdominal wall, and allowed rapid hand removal and reinsertion. CONCLUSIONS: Our preliminary results indicate that a hand assisted laparoscopic radical nephrectomy with the abdominal wall sealing device is an effective and safe surgical procedure, and is less invasive than open radical nephrectomy.

Adult↗

[Anatomical variations of Koch's triangle in patients with atrioventricular nodal reentrant tachycardia: usefulness of the left anterior oblique view].

OBJECTIVES: Several anatomical distances of Koch's triangle including the ablation site were measured and correlated with clinical features and slow pathway potentials in patients with atrioventricular nodal reentrant tachycardia to improve the avoidance of complete atrioventricular block. METHODS: Sixty consecutive patients (24 males and 36 females, mean age 47 +/- 12 years) with successfully eliminated atrioventricular nodal reentrat tachycardia were studied. The distances between the His-bundle area and the base of the coronary sinus ostium (Dis HBE-CS) and the distances between the successful ablation site and the base of the CS ostium (Dis SP-CS) were measured in both right anterior oblique and left anterior oblique views, and used to define the dimensions of Koch's triangle. The relationship between the slow pathway potentials at the successful ablation site and anatomical distances was estimated. RESULTS: The Dis HBE-CS in the right anterior oblique view was negatively correlated with patient age (r = -0.759, p < 0.001) and body mass index. In contrast, the Dis HBE-CS in the left anterior oblique view had only weak correlations with patient age and body mass index. The mechanism of the short Dis HBE-CS in the right anterior oblique view in elderly obese patients tended to change the shape of the tricuspid annulus from a circle to an ellipse, compressed by the ascending aorta and diaphragma. The Dis SP-CS in the right anterior oblique view associated with the low frequency potential (Haissaguerre's slow pathway potential) was longer than that associated with the high frequency potential (Jackman's slow pathway potential). CONCLUSIONS: Elderly obese patients had shorter distances between the proximal His-bundle area and the base of the coronary sinus ostium in the right anterior oblique view. In contrast, the Dis HBE-CS in the left anterior oblique view was not so narrow. Therefore, slow pathway ablation can be performed safely without complicated complete atrioventricular block, using both the slow pathway potential guided approach and the anatomical guided approach, especially in the left anterior oblique view.

Adolescent↗

MDR1 gene overexpression and altered degree of methylation at the promoter region in bladder cancer during chemotherapeutic treatment.

Overexpression of the multidrug resistance 1 (MDR1) gene is closely associated with the clinical outcome of hematopoietic malignancies, but the alteration of its expression during chemotherapeutic treatment and the precise mechanism underlying MDR1 gene overexpression in solid tumors remains unclear. We determined the expression and degree of methylation at the promoter of the MDR1 gene in bladder cancer. The mRNA levels of the MDR1 gene were found to be markedly enhanced, 3.5- to 5.7-fold higher in bladder cancers after chemotherapeutic treatment than those in untreated primary tumors. The MDR1 gene was overexpressed in recurrent tumors in 89% of patients who showed rerecurrence, whereas overexpression was observed in 25% of the patients without re-recurrence. A statistically significant inverse correlation existed between MDR1 expression and the methylation of 5'CpG sites at the promoter in patients with bladder cancer after chemotherapeutic treatment, with the degree of methylation at several CpG sites, rather than other specific sites, involved in this regulation. Consistent with the increase in MDR1 expression, the frequency of patients with a hypermethylated promoter decreased to 50 and 17% after intravesical and systemic chemotherapy, respectively. Thus, overexpression of the MDR1 gene might be a prognostic marker for intravesical recurrence, whereas methylation of the promoter region negatively regulates MDR1 expression and the appearance of multidrug resistance mediated by P-glycoprotein in bladder cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Evidence for autoregulation of cystathionine gamma-synthase mRNA stability in Arabidopsis.

Control of messenger RNA (mRNA) stability serves as an important mechanism for regulating gene expression. Analysis of Arabidopsis mutants that overaccumulate soluble methionine (Met) revealed that the gene for cystathionine gamma-synthase (CGS), the key enzyme in Met biosynthesis, is regulated at the level of mRNA stability. Transfection experiments with wild-type and mutant forms of the CGS gene suggest that an amino acid sequence encoded by the first exon of CGS acts in cis to destabilize its own mRNA in a process that is activated by Met or one of its metabolites.

Amino Acid Sequence↗

Presence of ganglia within the prostatic capsule: ganglion involvement in prostatic cancer.

BACKGROUND: The presence of ganglia within the prostatic capsule (capsular ganglia) is a poorly understood phenomenon. If cancer invasion into or around ganglia is identified in a needle biopsy specimen, such a finding may be diagnosed as an extraprostatic extension. In this study, the presence of capsular ganglia was clarified. Furthermore, we discuss the significance of these ganglia in prostatic cancer patients. METHODS: The study group comprised a total of 42 patients, who had all undergone a radical prostatectomy for prostate adenocarcinoma with a relatively small volume. After surgery, the step-sectioned radical prostatectomy specimens were histologically evaluated. RESULTS: In 22 of 42 cases, capsular ganglia were recognized. With respect to the distribution of the capsular ganglia, the ganglia were most frequently observed at the posteriolateral aspect of the prostatic base. Morphologically there were no obvious differences between the capsular and periprostatic ganglia. Moreover, in 3 of 5 cases with cancer involvement into the capsular ganglia, such involvement was not predictive of extraprostatic extension. CONCLUSIONS: The presence of capsular ganglia needs to be clarified in prostatic cancer patients. Our findings therefore suggest that cancer involvement either in or around the ganglia should not be immediately interpreted as indicating an extraprostatic extension, if such a finding is recognized in a needle biopsy specimen.

Adenocarcinoma↗

Use of bone turnover marker, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), in the assessment and monitoring of bone metastasis in prostate cancer.

BACKGROUND: We investigated whether a new marker of bone turnover, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), could be useful in the assessment of bone metastasis and in monitoring of the response to treatment in patients with prostate cancer with bone metastasis. METHODS: In all, 58 patients with prostate cancer (25 with bone metastasis and 33 without bone metastasis) and 52 patients with benign prostate hypertrophy who were treated between June 1994-August 1997 were included in this study. All patients were newly diagnosed. RESULTS: Serum ICTP levels in patients with prostate cancer with bone metastasis were significantly higher than those in patients with prostate cancer without bone metastasis (P<0.0001) or with benign prostate hypertrophy (P<0.0001). No significant differences were observed in serum ICTP levels between patients with prostate cancer without bone metastasis and those with benign prostate hypertrophy. Serum ICTP levels correlated significantly with Soloway's grading system for bone scans. Serum ICTP levels in patients with bone metastasis showed a significant downward trend in response to hormonal treatment. CONCLUSIONS: The determination of serum ICTP levels is useful in the assessment of bone metastasis and in monitoring the response of bone metastasis to treatment to prostate cancer.

Aged↗

Overexpression of the wild type p73 gene in human bladder cancer.

p73, a first p53 relative, was recently identified and shown to be monoallelically expressed in a number of different human tissues. To determine the potential role of this gene in human bladder cancer, we investigated p73 expression levels, allelic expression patterns, and analysed p73 mutations in 23 unselected primary invasive bladder cancers with matched normal tissues and in seven bladder cancer cell lines. In a comparison between normal and tumor tissues using quantitative RT-PCR analysis, we found that p73 was overexpressed in 22/23 bladder cancers, sometimes as great as 20-fold. Allelic expression analysis using a C/T polymorphism in exon 2 and a newly identified T/C polymorphism in exon 5 revealed that p73 was biallelically expressed in both normal bladder and cancer tissues, suggesting that p73 is not imprinted in bladder tissue. Mutation screening of the p73 gene in bladder cancer DNAs using denaturing high-performance liquid chromatography analysis and DNA sequencing revealed no tumor-specific mutations in any coding exons of the p73 gene. These data suggest that the p73 is unlikely to be a tumor suppressor gene, but that overexpression of p73 may contribute to tumorigenesis in bladder cancer.

Alleles↗

MR detection of cytoplasmic fat in clear cell renal cell carcinoma utilizing chemical shift gradient-echo imaging.

We attempted to determine whether cytoplasmic fat in clear cell renal cell carcinoma (RCC) can be identified by chemical shift gradient-echo magnetic resonance imaging (CSI). CSI was performed for 22 clear cell RCCs and 30 other renal tumors (including 16 non-clear cell RCCs), all of which were surgically proven. Signal reduction in out-of-phase images of these tumors was retrospectively evaluated and compared. The signal loss ratio (SLR) was defined and calculated. Fat staining of specimens from 16 tumors was performed and correlated with SLR. SLR was significantly higher in clear cell RCCs than in non-clear cell RCCs (P < 0.001). There was a significant correlation between degree of fat staining positivity of the specimens and SLR (P < 0.01). When signal reduction in out-of-phase images suggested the diagnosis of clear cell RCC, correct diagnosis of this entity was made in resected renal tumors with sensitivity, specificity, and accuracy of 82%, 90%, and 87%, respectively. CSI can demonstrate cytoplasmic fat in clear cell RCCs, which helps to differentiate this entity from other RCCs.

Adenocarcinoma, Clear Cell↗

Role of O-acetyl-l-serine in the coordinated regulation of the expression of a soybean seed storage-protein gene by sulfur and nitrogen nutrition.

The composition of seed storage proteins is regulated by sulfur and nitrogen supplies. Under conditions of a low sulfur-to-nitrogen ratio, accumulation of the beta-subunit of beta-conglycinin, a sulfur-poor seed storage protein of soybean (Glycine max [L.] Merr.), is elevated, whereas that of glycinin, a sulfur-rich storage protein, is reduced. Using transgenic Arabidopsis thaliana [L.] Heynh., it was found that the promoter from the gene encoding the beta-subunit of beta-conglycinin up-regulates gene expression under sulfur deficiency and down-regulates gene expression under nitrogen deficiency. To obtain an insight into the metabolic control of this regulation, the concentrations of metabolites related to the sulfur assimilation pathway were determined. Among the metabolites, O-acetyl-l-serine (OAS), one of the precursors of cysteine biosynthesis, accumulated to higher levels under low-sulfur and high-nitrogen conditions in siliques of transgenic A. thaliana. The pattern of OAS accumulation in response to various levels of sulfur and nitrogen was similar to that of gene expression driven by the beta-subunit promoter. Elevated levels of OAS accumulation were also observed in soybean cotyledons cultured under sulfur deficiency. Moreover, OAS applied to in-vitro cultures of immature soybean cotyledons under normal sulfate conditions resulted in a high accumulation of the beta-subunit mRNA and protein, whereas the accumulation of glycinin was reduced. These changes were very similar to the responses observed under conditions of sulfur deficiency. Our results suggest that the level of free OAS mediates sulfur- and nitrogen-regulation of soybean seed storage-protein composition.

Antigens, Plant↗

Stimulation of in vitro angiogenesis by hydrogen peroxide and the relation with ETS-1 in endothelial cells.

The purpose of this study was to examine the effect of hydrogen peroxide (H2O2) on angiogenesis in cultured endothelial cells. Endothelial cells obtained from bovine thoracic aorta (BAECs) were cultured between two layers of collagen type I to measure the tube formation which is a marker for angiogenesis. Addition of H2O2 (0.1-10 microM) to endothelial cells for various periods increased the rate of tube formation. The maximum stimulation of the tube formation was obtained when cells were exposed to 1 microM H2O2 for 30 min, and the enhancement of tube formation was blocked by catalase (10 U/ml). Both proliferation and migration of BAEC which are known to affect angiogenesis, were also stimulated by the addition of H2O2 (0.1 and 1 microM). Thus relatively low concentrations of H2O2 stimulated angiogenesis, proliferation and migration. Ets-1 is a member of the ets gene family of transcription factors, which binds to the ets binding motif in the cis-acting elements and regulates the expression of certain genes such as proteases including urokinase plasminogen activator (u-PA) and matrix metalloproteinase-1 (MMP-1). Interestingly, H2O2 increased the ets-1 mRNA level in BAECs compared with the basal level. The H2O2-stimulated angiogenesis was completely blocked by an ets-1 antisense oligonucleotide, but not by a mismatched oligonucleotide. These findings indicate that low concentrations of H2O2 stimulate angiogenesis in BAECs, and the stimulation mechanisms may partially involve the enhancement of proliferation and migration. Moreover, the H2O2-induced angiogenesis is likely to be mediated by the transcription factor ets-1.

Animals↗

Importance of intrathymic mixed chimerism for the maintenance of skin allograft tolerance across fully allogeneic antigens in mice.

In B6 (H-2b) mice that had been given, neonatally, 1x108 B6AKF1 spleen cells intraperitoneally (i.p.), only a moderate prolongation of donor (AKR:H-2k) skin graft survival was observed. In such B6 mice, no mixed lymphocyte reaction (MLR) to AKR could be detected on day 35 (35 days after birth), but it was clearly evident on day 84. Similarly, neither Vbeta6+ (reactive to MTV-7-encoded antigens) nor Vbeta11+ (reactive to I-E+MTV-derived superantigens) T cells were detected on day 35, but both were clearly evident on day 84 in both the thymus and the lymph nodes, thus indicating the breakdown of intrathymic mixed chimerism at the antigen-presenting cell level. Furthermore, by day 84, all skin grafts from AKR had already been rejected in such B6 mice. In the periphery, however, Vbeta6+, but not Vbeta11+, T cells were clonally anergic on day 84, based on a stimulation assay with anti-T-cell receptor (TCR) monoclonal antibody (mAb), thus suggesting that tolerance to some antigens, but not to others, may be induced by the clonal anergy in fully allogeneic combinations, and that the clonal anergic state may be masked by other proliferative responses. These results therefore indicate the importance of intrathymic mixed chimerism (central tolerance) and the limitations of clonal anergy (peripheral tolerance) in maintaining tolerance across fully allogeneic antigen barriers.

Animals↗

Mechanisms of drug resistance in chemotherapy for urogenital carcinoma.

Cancer chemotherapy is the principal approach for urogenital cancers. However, the acquisition of resistance to anticancer agents is a critical factor that limits the successful treatment of malignancies. The multidrug resistant (MDR) phenotype has been widely recognized in cancer chemotherapy in urogenital tumors and the mechanisms underlying MDR have also been extensively studied. One of the principle mechanisms in MDR is caused by the overexpression of P-glycoprotein (P-gp), encoded by the multidrug resistance gene (MDR1). It functions as an ATP-dependent active efflux pump of chemotherapeutic agents in human cancer cells. Recently, other drug resistance proteins, including multidrug resistance-associated protein (MRP1) and cMOAT (or MRP2), were also identified from multidrug resistant cells. A functional analysis of MRP1 has shown that MRP1 may have the potential to act as a transporter of glutathione conjugates, which has been known as a central detoxification pathway in anticancer agents. Furthermore, several other resistance-related proteins (e.g. glutathione S-transferase, metallothionein, thioredoxin, topoisomerase I, II, O6-alkylguanine-DNA methyltransferase, etc.) have been found to be up- or down-regulated in resistant cells and these molecules are believed to contribute to the resistant phenotype as well. Based on the molecular characteristics identified in MDR, several experimental and clinical approaches have been studied to overcome MDR. One of these strategies is to reverse MDR by using such P-gp inhibitors as verapamil and cyclosporine A. In this review, we summarize the recent advances in MDR-related molecules and clinical trials to circumvent MDR in urogenital carcinomas.

ATP Binding Cassette Transporter, Subfamily B↗

An analysis of risk factors for upper urinary tract deterioration in patients with myelodysplasia.

OBJECTIVE: To identify the risk factors for upper urinary tract deterioration in a retrospective study of patients with myelodysplasia. PATIENTS AND METHODS: The medical history, radiographic studies and urodynamic results from 39 children with myelodysplasia who were treated at our hospital were reviewed retrospectively to obtain more accurate data in the prognosis of such patients. The upper urinary tracts were assessed by cysto-urethrography and excretory urography to determine the incidence of vesico-ureteric reflux (VUR) and hydronephrosis. The relationships between the urodynamic variables, including vesical compliance, detrusor hyper-reflexia, detrusor-sphincter dyssynergia (DSD) and the maximum urethral closing pressure (MUCP) to such upper tract deterioration were evaluated using both univariate and multiple logistic regression analysis. RESULTS: The univariate analysis showed low vesical compliance, a high level of MUCP and the presence of DSD to be significant factors for the incidence of VUR. Low vesical compliance and a high level of MUCP also correlated with the incidence of hydronephrosis. The multivariate analysis showed a significant relationship between urodynamic values and upper urinary tract deterioration. The incidence of VUR was strongly correlated with a high MUCP and the presence of DSD. A high MUCP was also a significant factor in the incidence of hydronephrosis. CONCLUSION: Urodynamic results associated directly with the abnormal function of urethral control are significantly correlated with the cause of upper tract deterioration in patients with myelodysplasia.

Adolescent↗

Expression of the Axl receptor tyrosine kinase in human thyroid carcinoma.

Protein tyrosine kinases (PTKs) play a crucial role in regulating thyroid cell growth and differentiation. The Axl protein is a member of a new family of receptor tyrosine kinases, of which the ligand, Gas6, a protein S-related molecule, recently was proved to be a mitogenic factor for human thyroid cells. To further investigate the involvement of Axl in human thyroid carcinoma, we examined tissues obtained from 81 patients with thyroid carcinomas, 18 with adenomas, and 13 with adenomatous goiters by immunohistochemistry and in situ hybridization. In addition, among the thyroid carcinomas, we compared Axl expression levels with the grade of differentiation and lymph node metastasis of the carcinoma. Axl was expressed faintly in adenomatous goiter and adenomas, but not in normal thyroid tissues. Among the 81 cases of thyroid carcinoma, 70 (86.4%) showed a positive staining for the Axl protein. Immunopositive (+ +) was detected in papillary carcinomas and anaplastic carcinomas. The level of Axl expression, however, had no correlation with the presence of lymph node metastasis in thyroid carcinomas. In situ hybridization also confirmed the presence of axl mRNA in thyroid carcinoma tissues. These findings suggest that Axl expression may be closely involved in human thyroid tumorigenesis.

Adenoma↗